Computational design for improving the affinity of peptide ligands for carbohydrate-binding
Diarrhoeal diseases pose a serious global problem, especially in the developing world. Shigella flexneri Y, the most deadly species of Shigella, is endemic in most developing countries. An antibody, SYA/J6, against Shigella flexneri Y was developed. Studies have shown that MDWNMHAA is a weakly immunogenic peptide against the antibody SYA/J6. The research team at Zymeoworks Inc., a computational biotechnology company, is hoping to improve the binding of MDWNMHAA to SYA/J6 in order to generate a more effective immune response. This could lead to a vaccine for Shigella flexneri Y. The MITACS Accelerate intern, a Ph.D. student, will modify the structure of MDWNMHAA via mutagenesis, which involves the replacement of one amino acid for another. She will then evaluate and optimize the binding properties of the newly designed molecules using molecular dynamics simulations and other computational tools. Guidance and resources for these studies will be provided by Zymeworks, Inc.